TY - INPR UR - https://doi.org/10.1007/s00259-021-05192-8 N1 - This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. N2 - Purpose: To examine associations between the APOE-?2 and APOE-?4 alleles and core Alzheimer?s disease (AD) pathological hallmarks as measured by amyloid-? (A?) and tau PET in older individuals without dementia. Methods: We analyzed data from 462 ADNI participants without dementia who underwent A? ([18F]florbetapir or [18F]florbetaben) and tau ([18F]flortaucipir) PET, structural MRI, and cognitive testing. Employing APOE-?3 homozygotes as the reference group, associations between APOE-?2 and APOE-?4 carriership with global A? PET and regional tau PET measures (entorhinal cortex (ERC), inferior temporal cortex, and Braak-V/VI neocortical composite regions) were investigated using linear regression models. In a subset of 156 participants, we also investigated associations between APOE genotype and regional tau accumulation over time using linear mixed models. Finally, we assessed whether A? mediated the cross-sectional and longitudinal associations between APOE genotype and tau. Results: Compared to APOE-?3 homozygotes, APOE-?2 carriers had lower global A? burden (?std [95% confidence interval (CI)]: ? 0.31 [? 0.45, ? 0.16], p = 0.034) but did not differ on regional tau burden or tau accumulation over time. APOE-?4 participants showed higher A? (?std [95%CI]: 0.64 [0.42, 0.82], p < 0.001) and tau burden (?std range: 0.27-0.51, all p < 0.006). In mediation analyses, APOE-?4 only retained an A?-independent effect on tau in the ERC. APOE-?4 showed a trend towards increased tau accumulation over time in Braak-V/VI compared to APOE-?3 homozygotes (?std [95%CI]: 0.10 [? 0.02, 0.18], p = 0.11), and this association was fully mediated by baseline A?. Conclusion: Our data suggest that the established protective effect of the APOE-?2 allele against developing clinical AD is primarily linked to resistance against A? deposition rather than tau pathology. AV - public JF - European Journal of Nuclear Medicine and Molecular Imaging SN - 1619-7089 EP - 13 KW - Science & Technology KW - Life Sciences & Biomedicine KW - Radiology KW - Nuclear Medicine & Medical Imaging KW - Tau KW - Amyloid-beta KW - Cross-sectional KW - Longitudinal KW - Sex interaction KW - Cognition KW - Hippocampal volumes KW - APOE KW - PET Y1 - 2021/02/01/ TI - Differential associations of APOE-epsilon 2 and APOE-epsilon 4 alleles with PET-measured amyloid-beta and tau deposition in older individuals without dementia A1 - Salvado, G A1 - Grothe, MJ A1 - Groot, C A1 - Moscoso, A A1 - Scholl, M A1 - Gispert, JD A1 - Ossenkoppele, R ID - discovery10122931 PB - SPRINGER ER -